Studies in our laboratory have focused on defining the nature of the B cell defects in the disease, Common Variable Immunodeficiency (CVI), a primary acquired human immunodeficiency state characterized by hypogammaglobulinemia (low levels of immunoglobulin in the serum), and impaired functional antibody responses. Our previous studies of purified B cells from CVI patients show that although the cells have a normal capacity to proliferate, they manifest differentiation defects at multiple levels. For example, when compared to normal B cells, circulating CVI B cells contain reduced numbers of surface bearing IgG and IgA cells with a commensurate increase in surface bearing IgM B cells, suggesting an in vivo defect in isotype switch. In addition, these cells fail to undergo differentiation into immunoglobulin producing cells. During this period we have initiated the study of CVI B cells with respect to their expression of transcription factors and cofactors known to be necessary for B cell switching and terminal differentiation. In particular, we have focused on the B cell-specific transcription factor, Oct-2, sine mice lacking this protein as a result of gene targeting have a phenotype similar to that of patients with CVI. In initial studies, we prepared RNA from purified B cells of patients and controls following stimulation with SAC plus IL-2 and amplified the RNA by RT-PCR using primers specific for the Oct-2 gene. CVI patient and control RNA gave rise to identical signals indicating no gross abnormality in the expression of Oct-2 RNA. We then evaluated Oct-2 protein function by performing electrophoretic mobility shift assays using the nuclear extracts of stimulated fresh B cells from patients and controls, as well as EBV-transformed B cell lines from patients and controls. The target oligonucleotide utilized was that of the core Oct-2 promoter site. We found that extracts from both patients and controls yielded an EMSA signal of appropriate size and identical intensity. These results indicate that CVI B cells do not manifest a gross deletion of the Oct-2 gene, nor do they manifest an abnormality of Oct-2 binding to the core Oct-2 promoter site.